In diabetes mellitus, dysfunctional endothelial cells (EC) and low numbers of endothelial progenitor cells (EPC) in the peripheral circulation lead to several vascular disorders like impaired wound healing. Recent reports indicate reactive oxygen species (ROS) and low expression of the cytokine, stromal cell-derived factor-1 (SDF-1) to be important causes of these pathological conditions. As neurotransmitter dopamine (DA) is reported to regulate ROS production and because DA may also control SDF-1 synthesis, we therefore hypothesized that DA could normalize EC functions and SDF-1 expression in diabetic wound tissues. Aim 1 will investigate the effect of DA D1 receptors on ROS induced EC functions. In Aim 2, the role of DA D1 receptors on SDF-1 production by macrophages will be determined and finally Aim 3 will examine the effects of DA D1 receptors on ROS production and neovascularization in diabetic wound tissues. PUBLIC HEALTH RELEVANCE: Endothelial cell dysfunctions and significantly decreased production of growth factors and cytokines in diabetes mellitus lead to several vascular disorders like impaired wound repair and healing. According to the Center for Disease Control and Prevention, refractory diabetic wounds lead to over 72,000 amputations each year despite of advances in wound care, therefore the goal of this application is to develop dopamine mediated newer and an effective therapy for this pathological condition.